The goals of this research are to develop a better understanding of the factors responsible for the "aging" of skin produced by actinic damage and by chronologically aging. The elastic fiber network and the microvasculature will be specifically investigated. Skin biopsies from volunteers will provide material for these studies: sun-exposed and sun-protected skin from young and aged healthy persons, and from juvenile and mature onset diabetics. Elastogenesis in human skin will be studied with the combined use of transmission EM, scanning EM and 3-dimensional reconstructions by computer graphics. Antibodies against elastin and elastic microfibrils will be used to identify the two components of the elastic fiber in these studies. By the same combination of techniques, the sequential morphological events involved in actinic elastosis and in the degenerative changes associated with chronological aging will be systematically studied. Employing in vitro autoradiography and pulse chase experiments on skin biopsies investigations will be performed to determine whether there are 2 types of fibroblasts in skin--one synthesizing collagen and the other elastin. Serum and fluid from suction blisters of forearm and buttock skin obtained from volunteers in these various groups will be tested for elastase activity using synthetic substrates. These studies will test a variety of hypotheses related to the formation and degradation of elastic fibers in human skin. Studies will also be carried out to determine whether degenerative elastic fiber changes in buttock skin can be correlated with those in the lung and whether the skin can be used as a predictor of a systemic aging process. The ultrastructural features of all the segments of the microvasculature from arterioles through capillary bed to venule will be defined both for aged skin and for actinically damaged skin. These studies should provide information that is not only applicable to aging skin but also to the aging lung, diabetes and atherosclerosis.